Lipid-polymer hybrid nanocarrier-mediated cancer therapeutics: current status and future directions.

The new generation of nanoparticles (NPs) encompass attributes of lipids and polymers and are referred to as 'lipid-polymer hybrid nanoparticles' (LPHNPs). LPHNPs have helped shed light on the mechanisms involved in targeted and non-specific drug delivery. Research has also highlighted the opportunities and challenges faced by the use of nanomedicine as personalized therapies in oncology. Here, we review the development of LPHNPs as cancer therapeutics, focusing on the methods deployed for enhancing the targeting efficiency and applications of LPHNPs.

Current State of Nanomedicines in the Treatment of Topical Infectious Disorders.

BACKGROUND: Topical infections, involving a number of diseases such as impetigo, eczema, pustular acne, psoriasis and infected seborrheic dermatitis are one among the many challenges to health which stand out for their profound impact on human species. The treatment of topical infections has always been a difficult proposition because of the lack of efficacy of existing anti-infectives, longer period of treatment and yet incomplete recovery. The increasing emergence of antibiotic resistant bacterial strains like Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa undermines the need for the development of new delivery systems to enhance the therapeutic efficacy of existing topical anti-infectives. METHODS: The application of nanotechnology to medicine, or nanomedicine, is rapidly becoming a major driving force behind ongoing changes in the anti-infective field because of its interaction at the sub-atomic level with the skin tissue. The latter, in the current scenario, points towards vesicular carriers like liposomes, lipidic nanoparticles and silver nanoparticles. as the most promising drug delivery solutions for topical infection disorders. These have exhibited immense significance owing to their uniqueness to facilitate the interactions at interfaces with the barrier membranes. RESULTS: The present review summarizes the emerging efforts in combating topical infections particularly using nanomedicine based delivery systems as new tools to tackle the current challenges in treating infectious diseases. Besides, compiling various research reports, this article also includes formulation considerations, mechanisms of penetration and patents reported. CONCLUSION: Despite the new emerging technologies and delivery systems, efforts are still needed in the right direction to combat this global challenge.

Cationic-bilayered nanoemulsion of fusidic acid: an investigation on eradication of methicillin-resistant Staphylococcus aureus 33591 infection in burn wound.

AIM: The aim of the current study was to investigate the therapeutic efficacy of cationic-charged bilayered nanoemulsion for topical delivery of fusidic acid in eradicating methicillin-resistant Staphylococcus aureus (MRSA) bacterial burn wound infection. MATERIALS & METHODS: The developed carriers were characterized for particle size, antibacterial activity, cell viability assay in HaCat cell lines, rheological profile, ex vivo and in vivo studies, namely, full thickness MRSA 33591 murine burn wound infection via topical route. RESULTS: The developed cationic bilayered nanogel offered enhanced drug permeation, reduction in bacterial load and enhanced wound contraction along with faster re-epithelialization in burn wounds. CONCLUSION: The results encourage the exploration of the potential of cationic nanogel in treating resistant microorganisms such as MRSA, especially for application in burn wound infection.

Thymoquinone a Potential Therapeutic Molecule from the Plant Nigella sativa: Role of Colloidal Carriers in its Effective Delivery.

BACKGROUND: From the past few decades, remarkable awareness has laid on the use of herbal medicines in pharmaceutical research. Thymoquinone (TQ), the main chemical constituent of Nigella Sativa (NS) plant, has been extensively explored, and revealed an array of therapeutic benefits, in different in vitro, and in vivo conditions. This review provides brief outline of the diverse therapeutics actions of TQ, and NS, viz. anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, gastroprotective, hepato-protective, anti-microbial and anti-histaminic. Besides, a special emphasis has given on the use of colloidal drug delivery systems exploited hitherto, for the effective delivery of TQ and NS. OBJECTIVE: The main objective of the review was to include an intensive patent literature, available on TQ and NS, for its usefulness in different therapeutic conditions. METHODS: We embarked an organized search of bibliographic databases for peer-reviewed research literature and patent databases. The characteristics of screened papers were described, and a rational qualitative content analysis approach was applied to analyze the interventions and findings of included studies using a theoretical framework. RESULTS: In the past, various studies have carried out which undoubtedly vouch for the multifarious therapeutic roles of TQ in an array of different diseases. More than 670 research papers and around 50 review articles are available on TQ and NS in PubMed database until now, suggesting its high significance. Around 12 review articles published only on the anticancer potential, while the others on its anti- inflammatory and anti-oxidant potential. Around 120 papers included in the review revealed the therapeutic benefits of TQ. In addition to this, an intensive patent literature is also available on TQ and NS, for its usefulness in different therapeutic conditions. CONCLUSION: The findings of this review confirm the effectiveness of TQ in various pathologies viz. inflammation, cancer, diabetes, gastric, hepatic, microbial and allergies. However, the complete clinical benefit of TQ has not yet been realized, owing to its poor biopharmaceutical properties. Nevertheless, colloidal drug delivery carrier systems, could be impending in bringing forth this potential molecule to reality.

Self-assembly of aromatic α-amino acids into amyloid inspired nano/micro scaled architects.

In the pursuit for design of novel bio inspired materials, aromatic α-amino acids (phenylalanine, tyrosine, tryptophan and histidine) have been investigated for the generation of well-ordered self-assembled architects such as fibrils, rods, ribbons and twisted nanosheets in varying solvent systems. These nano/micro scaled architects were thoroughly characterized using FE-SEM, confocal microscopy, optical microscopy, 1H NMR, FTIR, XRD and TGA. These self-assembled architects were histologically stained with Congo red and thioflavin T dyes for investigation of amyloid morphology which revealed that the deposited state of ordered assemblies exhibit specific characteristic of amyloid deposits. The self-assembly of aromatic amino acids was observed to be driven by non-covalent forces such as π-π stacking, van der Waals and electrostatic interaction.

QbD-Based Development and Validation of a Stability-Indicating HPLC Method for Estimating Ketoprofen in Bulk Drug and Proniosomal Vesicular System.

The current studies entail systematic quality by design (QbD)-based development of simple, precise, cost-effective and stability-indicating high-performance liquid chromatography method for estimation of ketoprofen. Analytical target profile was defined and critical analytical attributes (CAAs) were selected. Chromatographic separation was accomplished with an isocratic, reversed-phase chromatography using C-18 column, pH 6.8, phosphate buffer-methanol (50 : 50v/v) as a mobile phase at a flow rate of 1.0 mL/min and UV detection at 258 nm. Systematic optimization of chromatographic method was performed using central composite design by evaluating theoretical plates and peak tailing as the CAAs. The method was validated as per International Conference on Harmonization guidelines with parameters such as high sensitivity, specificity of the method with linearity ranging between 0.05 and 250 µg/mL, detection limit of 0.025 µg/mL and quantification limit of 0.05 µg/mL. Precision was demonstrated using relative standard deviation of 1.21%. Stress degradation studies performed using acid, base, peroxide, thermal and photolytic methods helped in identifying the degradation products in the proniosome delivery systems. The results successfully demonstrated the utility of QbD for optimizing the chromatographic conditions for developing highly sensitive liquid chromatographic method for ketoprofen.

Sterically stabilized gelatin microassemblies of noscapine enhance cytotoxicity, apoptosis and drug delivery in lung cancer cells.

Noscapine, recently identified as anticancer due to its microtubule-modulating properties. It is presently in Phase I/II clinical trials. The therapeutic efficacy of noscapine has been established in several xenograft models. Its pharmacokinetic limitations such as low bioavailability and high ED50 impede development of clinically relevant treatment regimens. Here we present design, synthesis, in vitro and in vivo characterization of sterically stabilized gelatin microassemblies of noscapine (SSGMS) for targeting human non-small cell lung cancer A549 cells. The average size of the sterically stabilized gelatin microassemblies of noscapine, SSGMS was 10.0±5.1 µm in comparison to noscapine-loaded gelatin microassemblies, GMS that was 8.3±5.5 µm. The noscapine entrapment efficiency of SSGMS and GMS was 23.99±4.5% and 24.23±2.6%, respectively. Prepared microassemblies were spherical in shape and did not show any drug and polymer interaction as examined by FTIR, DSC and PXRD. In vitro release data indicated that SSGMS and GMS follow first-order release kinetics and exhibited an initial burst followed by slow release of the drug. In vitro cytotoxicity evaluated using A549 cells showed a low IC50 value of SSGMS (15.5 µM) compared to GMS (30.1 µM) and free noscapine (47.2 µM). The SSGMS can facilitate a sustained therapeutic effect in terms of prolonged release of noscapine as evident by caspase-3 activity in A549 cells. Concomitantly, pharmacokinetic and biodistribution analysis showed that SSGMS increased the plasma half-life of noscapine by ~9.57-fold with an accumulation of ~48% drug in the lungs. Our data provides evidence for the potential usefulness of SSGMS for noscapine delivery in lung cancer.

Nanosolvated microtubule-modulating chemotherapeutics: a case-to-case study.

About 10% of the drugs in the preclinical stage are poorly soluble, 40% of the drugs in the pipeline have poor solubility, and even 60% of drugs coming directly from synthesis have aqueous solubility below 0.1 mg/ml. Out of the research around, 40% of lipophilic drug candidates fail to reach the market despite having potential pharmacodynamic activities. Microtubule-modulating chemotherapeutics is an important class of cancer chemotherapy. Most chemotherapeutics that belong to this category are plant-derived active constituents, such as vincristine, vinblastine, colchicine, docetaxel, paclitaxel, and noscapinoids. The pKa of a drug considerably affects its solubility in physiological fluids and consequently bioavailability. It usually ranges from 5 to 12 for microtubule-modulating drugs. Hence, the solubility of these drugs in physiological fluids is considerably affected by a change in pH. However, because of unpredictable parameters involved in poor solubility and the low oral bioavailability of these chemotherapeutics during the early phases of drug development, they often have an unusual pharmacokinetic profile. This makes the development process of novel chemotherapeutics slow, inefficient, patient-unfriendly, and very costly, emphasizing a need for more rational approaches on the basis of preclinical concepts. Nanosolvation is a process of increasing the polarity of a hydrophobic molecule either by solvation or cavitization in a hydrophilic macrocycle. The present review therefore focuses on the techniques applied in nanosolvation of microtubule-modulating chemotherapeutics to enhance solubility and bioavailability. The methodologies described will be highly beneficial for anticancer researchers to follow a trend of rational drug development.

A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis.

Dithranol is infrequently used in psoriasis in spite of excellent efficacy due to its local adverse effects. We have synthesized a novel formulation of dithranol in which the drug is entrapped in phospholipid liposomes. This formulation has shown markedly low irritation and minimal staining of skin and clothes in preliminary studies. Twenty patients with bilaterally symmetrical stable plaque psoriasis applied 0.5% dithranol lipogel to lesions over one side of the body. On the other side, 10 patients were randomized to apply pure liposomal base and 10 applied a conventional cream containing 1.15% dithranol, 1.15% salicylic acid and 5.3% coal tar in a 30-minute, short contact regimen for 6 weeks. Patients were assessed for disease severity, perilesional erythema and skin staining, pruritus and any other adverse effects at baseline, 2, 4 and 6 weeks. Both lipogel and the cream significantly reduced the total severity score compared to the liposomal base at 4 (p = 0.004) and 6 (p = 0.01) weeks. There was no significant difference in the clinical response of dithranol cream and lipogel. Markedly low incidence and severity of perilesional erythema (p<0.001) and skin staining (p<0.05) was seen with the lipogel in comparison with the cream.